Thesis (S.M.)--Harvard-MIT Program in Health Sciences and Technology, 2013. / Vita. Cataloged from PDF version of thesis. / Includes bibliographical references (pages 37-39). / Clinical x-ray mammography cannot delineate between hydroxyapatite and calcium oxalate, the respective forms of calcification in malignant and benign breast tumors. The water-poor nature of solid calcifications makes them difficult to image by conventional MRI. Recently, ultra-short echo time (UTE) MRI has enabled detection of solid calcified structures, but it is not specific to the underlying chemical composition. This thesis presents a hydroxyapatite-targeted gadolinium contrast agent for UTE MRI of calcification in malignant breast cancer. The hydroxyapatite-targeted contrast agent was synthesized by conjugating a bisphosphonate, pamidronate, to a gadolinium chelate. Binding specificity was tested by UTE MRI of the contrast agent reacted with hydroxyapatite, calcium oxalate, and other calcium-based crystals. The sensitivity of the contrast agent for hydroxyapatite was evaluated by UTE MRI: the lowest detectable concentration of hydroxyapatite-adsorbed contrast was 1 pM. Longitudinal relaxation time measurements were used to estimate the apparent relaxivity of the hydroxyapatite contrast agent to be >1000 s-I/mM. The targeted agent relaxivity is enhanced more than a 100-fold compared to conventional untargeted gadolinium contrast agents due to the restricted rotational motion of the contrast agent upon binding to a solid surface. In-vivo MRI of systemic delivery of the contrast agent was demonstrated in an animal model for breast cancer with hydroxyapatite calcifications. Pre- and post-contrast UTE MRI were acquired with systemic contrast agent injections. Dual-echo UTE subtraction images between short and long echoes showed specific uptake of the contrast agent to the calcifications. The mean signal intensity of the calcified regions enhanced by 200% between pre- and post-contrast images, posing the hydroxyapatite-targeted contrast agent as a clinical diagnostic for distinguishing benign and malignant calcification forms in breast cancer. / by Jonathan Marmurek. / S.M.
| Identifer | oai:union.ndltd.org:MIT/oai:dspace.mit.edu:1721.1/83969 |
| Date | January 2013 |
| Creators | Marmurek, Jonathan |
| Contributors | Robert E. Lenkinski and Bruce R. Rosen., Harvard--MIT Program in Health Sciences and Technology., Harvard--MIT Program in Health Sciences and Technology. |
| Publisher | Massachusetts Institute of Technology |
| Source Sets | M.I.T. Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 45 pages, application/pdf |
| Rights | M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission., http://dspace.mit.edu/handle/1721.1/7582 |
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